tbuckley/cabot-search huggingface dataset:
NeoIRX trial: Immunologic induction with peri-lymphatic cytokines to enhance pembrolizumab (pembro) response in stage II/III triple-negative breast cancer (TNBC).
Authors: David B. Page, Alan Su, Nicole Moxon, Staci L. Mellinger, Tracy Kelly, Alison Katherine Conlin, Zheng Zhu Topp, Pippa Newell, Nicole Fredrich, Kristen P. Massimino, Yaping Wu, William L Redmond, Shaghayegh Aliabadi, Zhaoyu Sun, James Imatani, Sasha E. Stanton
Journal: Journal of Clinical Oncology (2023)

604 Background: The addition of pembro to neoadjuvant chemotherapy (NACT) improves pathological complete response (pCR) rate and recurrence-free survival in stage II/III TNBC, albeit with substantial chemotherapy-attributed toxicity. We hypothesize that locoregional cytokine therapy could be combined with pembro to optimize immune response and clinical outcome. In a phase Ib early-stage breast cancer trial, we previously demonstrated that peri-lymphatic cytokine injection (IRX-2 regimen, comprised of physiologic doses of IL-2, IFNg, and other cytokines derived from activated donor lymphocytes, given with low-dose cyclophosphamide) is well tolerated and associated with increased intratumoral lymphocytes, T-cell activation, and PD-L1 expression. Here, we report preliminary outcomes of neoIRX, a phase II trial evaluating induction IRX-2 + pembro preceding NACT + pembro. Methods: Subjects with stage II/III TNBC were randomized to receive induction pembrolizumab (all subjects: 200mg IV) +/- peri-areolar IRX-2 (IRX-2 arm: 1 ml SQ x2 daily for 10 days + cyclophosphamide 300 mg/m2 IV x 1) preceding initiation of NACT + pembro. The primary endpoint was pCR rate following NACT + pembro (n = 15 subjects/arm planned); secondary endpoints were safety and tolerability. We explored post-induction/pre-NACT radiographic (ultrasound) and histologic outcomes (TILs, tumor regression) as a biomarker strategy to predict pCR. Results: The trial terminated after n = 12 subjects due to withdrawal of drug support for IRX-2. The IRX-2 arm achieved 83% pCR (n = 5/6, CI 36-100%) compared to 33% pCR with pembro alone (n = 2/6, CI 4-78%). The regimen was well-tolerated with minimal IRX-2-attributed toxicities (67% grade I skin bruise). Toxicities during NACT + pembro were similar to Keynote-522. 67% (n = 4/6) of IRX-2 subjects experienced week 3 radiographic regression, with evidence of brisk lymphocyte infiltration on week 3 biopsy, and with 100% pCR rate (n = 4/4) following NACT + pembro. n = 2/6 subjects receiving pembro+IRX-2 experienced pCR on week 3 biopsy, versus n = 0/3 evaluable in control arm. Conclusions: Induction IRX-2 + pembro is well tolerated and is associated with encouraging outcomes, supporting further study of peri-lymphatic induction cytokine therapy in stage II/III TBNC. Post-induction radiographic and histologic outcomes may identify patients with immune-responsive tumors, for whom NACT de-escalation may be a promising therapeutic approach to mitigate toxicity. Clinical trial information: NCT04373031 .
Actionability of comprehensive genomic profiling compared to the tissue-based and plasma-based assay in patients with metastatic breast cancer: A real-world study.
Authors: Hiroshi Tada, Jun Yasuda, Hidekazu Shirota, Minoru Miyashita, Narumi Harada-shoji, Yohei Hamanaka, Akiko Ebata, Miku Sato, Takanori Ishida
Journal: Journal of Clinical Oncology (2023)

1101 Background: Comprehensive genomic profiling (CGP) was officially approved in August 2021 in Japan under the national health insurance system with three CGP tests in June 2019: FoundationOne CDx (F1CDx), OncoGuide NCC Oncopanel (NCC), which are tissue-based assay (TBA), and FoundationOne Liquid CDx (F1LCDx, starting in August 2021) which is plasma-based panel (PBA). The Center for Cancer Genomics and Advanced Therapeutics (C-CAT) has collected genomic and clinical data of 2,617 Japanese breast cancer patients as of October 2022. Here we assess these PBA and TBA to detect pathogenic or driver alterations informative for matched therapy in patients with metastatic breast cancer (mBC). Methods: We queried consecutive mBC patient clinical-genomic data through the C-CAT Research-Use Portal from June 2019 to October 2022 were categorized based on PBA or TBA. We used ClinVar to identify if the called somatic alterations were pathogenic or likely pathogenic, and BoostDM (https://www.intogen.org/boostdm/search) to identify potential driver mutations of breast cancer. The proposed rate of matched therapy was determined. The incidence rates were compared using the Pearson χ2 test. Results: Of 2,617 pts who underwent the CGP test, 2,259 (86%) received TBA (74% F1CDx and 12% NCC). The proportion of pts with ≥1 pathogenic variant with PBA and TBA was not significant (71.5%vs.72.7%; p=0.88), but the proportion of pts with ≥1 driver mutation was significantly higher with PBA than TBA (75.4% vs. 69.8%; p = 0.03). Regarding the proportion of pts who matched therapy or clinical trials presented among the pts for whom data were available, PBA was significantly lower than TBA (27.7% vs.38.5%, p &lt; 0.001). Although data on post-treatment is still being collected, the proportion of tested patients that received matched therapies recommended by molecular tumor boards of each institute was significantly lower for PBA (4.2%vs. 8.3%; p = 0.007). Conclusions: This study is the first analysis of CGP for mBC in Japan using the C-CAT utilization program. Although significant alterations were well-detected in PBA, the proportion of pts who received matched-therapy post-testing was low for PBA. Possible causes include that PBA has fewer companion diagnoses than TBA in Japan and that PBA is more often used in later lines.
Early assessment of sotorasib for treatment of patients with advanced non-small cell lung cancer using real-world data in the United States.
Authors: Dvir Aran, Meishar Shahoha, Keren Rosenberg-Katz, Shlomit Amar-Farkash
Journal: Journal of Clinical Oncology (2023)

1560 Background: Sotorasib is the first small molecule for targeting tumors with KRAS G12C mutations. Despite promising early results which led to expedited approval, recent interim results from the phase III clinical trial suggest similar efficacy to standard-of-care chemotherapy docetaxel. Here we perform the first evaluation of sotorasib for the treatment of non-small cell lung cancer (NSCLC) in real-world setting. Methods: Elevance Health claims data was used. Lung cancer (LC) patients with sotorasib claims between June 2021-August 2022 were identified (assumed to be NSCLC). LC patients treated with docetaxel as second-line+ were used as control group. Potential confounding factors, including social determinant index (SDI), age, gender, Charlson Comorbidity Index (CCI), and metastases profile were addressed using inverse probability treatment weighting (IPTW). Outcomes were hospitalizations and real-world overall survival (rwOS), which was estimated using weighted Kaplan-Meier estimator. For comparison with the clinical trial population-level adjustments were performed. Results: Cohorts included 105 sotorasib-treated and 448 docetaxel-treated patients. Sotorasib-treated were primarily female, of older age and had more comorbidities. Posttreatment all-cause hospitalization rates were similar during the first 3 months (36% in both). Most common hospitalization diagnosis was gastrointestinal (GI) related which was uncommon in the control group (29% vs. 8%, p&lt;.001). No evidence for liver toxicity was identified. For a subset of patients it was possible to perform survival analysis. Adjusted survival curves of RWD and the clinical trial (CodeBreak-100) were indistinguishable following population-level adjustment (p=0.92). Adjusted RWD sotorasib and the control cohorts revealed non-significant difference in rwOS up to 6-months of follow-up (62% sotorasib vs. 55% docetaxel; p=0.1). Conclusions: We present the first analysis of sotorasib in US real-world settings. This early analysis suggests that sotorasib does not provide survival benefit at 6-months follow-up. Sotorasib is associated with increased GI-related severe adverse events. RWD can be used to provide early information in expedited FDA approved treatments. [Table: see text]
Amelioration of acute radiation dermatitis in patients with breast cancer by a bioadhesive barrier-forming oral gel (Episil): A single-center, open, parallel, randomized controlled trial.
Authors: Qian Li, Fangling Ning, Changmin Liu
Journal: Journal of Clinical Oncology (2023)

e12519 Background: Episil is a bioadhesive barrier-forming oral liquid gel that can relieve mucositis caused by radiotherapy (RT) and hence relieves pain effectively.The purpose of this trial is to compare the efficacy and safety of Episil in improving acute radiation dermatitis in breast cancer patients. Methods: Key eligibility criteria were as follows: Pathologically confirmed breast cancer; female ≥18 years of age; planning to receive postoperative radiation therapy; surgery with modified radical or breast-conserving surgery; fully healed surgical incision; intact skin in the irradiated area; KPS score ≥80; no severe endocrine or metabolic disease; voluntary participation and signed informed consent; ability to read and understand and good compliance. The primary endpoint was the grading of radiation dermatitis during treatment. Results: A total of 102 patients were included from January 2022 to December 2022. The patients were grouped in a 2:1 ratio by randomized number table method, 67 patients received Episil combined with conventional skin care and 35 patients served as the control group receiving conventional skin care only. Two patients in the Episil group dropped out halfway. According to the RTOG grading, the skin reaction rate and the degree were significantly better in the Episil group than control group (24.62%, 72.31%, 3.08, 0, 0 VS 0, 85.71%, 14.29%, 0, 0, 0) in the 0, 1, 2, 3 and 4 grades respectively (P&lt;0.001). And the pruritus score was significantly lower in the Episil group than in the control group (P&lt;0.05). The results of the EORTC QLQ-C30 Quality of Life Questionnaire showed that the overall health (P&lt;0.05) and overall quality of life (P&lt;0.05) were better in the Episil group than control group after radiotherapy. Relative to the control group, the Episil group produced significantly lower rates of stress, anxiety, and depression (P&lt;0.05) and had less impact on family life and social activities (P&lt;0.05). Most importantly, the Episil group produced fewer pain reactions after the end of radiotherapy. Conclusions: In breast cancer patients receiving radiotherapy, Episil may significantly reduce the grading of acute radiation dermatitis, reduce patient symptoms, and improve patient quality of life. Clinical trial information: ChiCTR2200059646 .
An age-specific pooled analysis of trastuzumab deruxtecan (T-DXd) in patients (pts) with HER2-positive (HER2+) metastatic breast cancer (mBC) from DESTINY-Breast01, -02, and -03.
Authors: Ian E. Krop, Hans Wildiers, Sara A. Hurvitz, Javier Cortes, Seock-Ah Im, Hiroji Iwata, Fabrice Andre, Cristina Saura, Shanu Modi, Sung-Bae Kim, Anton Egorov, Elton Mathias, Jillian Cathcart, Antonio Cagnazzo, Yingkai Cheng, Yeon Hee Park
Journal: Journal of Clinical Oncology (2023)

1006 Background: T-DXd is approved for use in pts with HER2+ unresectable or mBC after a prior anti-HER2-based regimen in the metastatic or (neo)adjuvant setting, based on the randomized phase 3 DESTINY-Breast03 study (Cortes et al. N Engl J Med 2022). Older pts with HER2+ mBC tend to have worse efficacy and safety outcomes, regardless of treatment (Evans et al. Cancer Res 2021). Outcomes of older pts treated with T-DXd have not been thoroughly examined. Here we report age-specific (&lt;65 vs ≥65 years) efficacy and pooled safety analyses of T-DXd from DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03. Methods: DESTINY-Breast01 (data cutoff [DCO], March 26, 2021) and DESTINY-Breast02 (DCO, June 30, 2022) enrolled pts whose disease progressed on trastuzumab emtansine (T-DM1); DESTINY-Breast02 compared T-DXd to chemotherapy of physician’s choice. DESTINY-Breast03 (DCO, July 25, 2022) included pts previously treated with trastuzumab and taxane; pts received either T-DXd or T-DM1. Results: At baseline, there were 44 (23.9%), 85 (20.9%), and 49 (18.8%) pts ≥65 years of age who received T-DXd in DESTINY-Breast01, DESTINY-Breast02, and DESTINY-Breast03, respectively. At DCO, median pooled treatment duration with T-DXd was 13.1 mo (range, 0.7-44.0) for pts &lt;65 and 12.4 mo (range, 0.7-45.1) for pts ≥65. Key efficacy data are shown in the Table. Any-grade treatment-emergent adverse events (TEAEs), grade ≥3 TEAEs, and serious AEs were observed in 99.6%, 53.6%, and 24.3% of pts &lt;65 and 100%, 65.5%, and 32.2% of pts ≥65, respectively. There were 125 (18.7%) and 45 (25.4%) TEAEs associated with T-DXd discontinuation in pts aged &lt;65 and ≥65, respectively. Any-grade adjudicated drug-related interstitial lung disease/pneumonitis occurred in 11.8% of pts &lt;65 and 17.5% of pts ≥65; grade 5 events occurred in 0.9% and 0.6% of pts &lt;65 and ≥65, respectively. Additional efficacy and safety data will be presented. Conclusions: Results from this pooled analysis further demonstrate that T-DXd has a favorable benefit-risk profile in pts ≥65 years, with slightly increased toxicity, as expected. Clinical trial information: NCT03248492 , NCT03523585 , NCT03529110 . [Table: see text]
Do HER2 low tumors have a distinct clinicopathologic phenotype?
Authors: Natália Polidorio, Srinivasa Sevilimedu Veeravalli, Giacomo Montagna, Tiana Le, Monica Morrow
Journal: Journal of Clinical Oncology (2023)

570 Background: Clinicopathologic features of breast cancer subtypes defined by hormone receptor (HR) and HER2 status differ. These analyses classified HER2 IHC &lt;3+ with negative FISH as HER2-. With the recognition of the clinical relevance of HER2 low, there is debate as to whether this is a distinct subtype. We sought to determine if features of HER2 low tumors differ from HER2- and HER2+ after controlling for HR status. Methods: Patients undergoing upfront surgery from 1998 to 2010 were identified from a prospectively maintained institutional database. HER2 status was classified by IHC/FISH analysis as HER2-, HER2 low (IHC 1+ or 2+ with negative FISH), and HER2+ (IHC 3+ or FISH +) and stratified by HR status. Univariable (UVA) and multivariable multinomial logistic regression analysis (MVA) were performed to determine associations among variables and subtypes. Results: 11,323 tumors from 11,072 patients were included. 5,104 (45%) were HER2 low, 41.2% were HER2- and 13.6% were HER2+. On MVA stratified by HER2 status only, compared to HER2- tumors, HER2 low was associated with LVI (OR 1.2 [95% CI 1.06-1.36]; p=.003), multifocality (OR 1.26 [95% CI, 1.12-1.42]; p&lt;.001), nodal micrometastasis (OR 1.15 [95% CI, 1.02-1.31]; p=.024), and lower rates of &lt;3 positive nodes (OR 0.77 [95% CI, 0.66-0.90], p=.001). HER2+ was associated with younger age, high grade, multifocality, extensive intraductal component (EIC), and pN2/3 nodal stage. Clinicopathologic features stratified by HR and HER2 status are shown in the table. On UVA, in both HR+ and HR– tumors, age and multifocality were associated with HER2 low, and LVI, multifocality, and EIC with HER2+ compared to HER2- tumors. On MVA, no variables were independently associated with both HR+ and HR-/HER2 low tumors compared to HER2-. In contrast, HER2+ tumors regardless of HR status were significantly associated with multifocality and EIC. Conclusions: HER2 low breast cancer features seem to be driven by HR status and HER2 overexpression. We do not have enough evidence to support the interpretation of HER2 low as a distinct subtype. [Table: see text]
CANKADO PRO-React eHealth support in patients with HR+ HER2- metastatic breast cancer receiving palbociclib and endocrine therapy and the affect on time to deterioration of quality of life: Primary outcome analysis of the multicenter randomized PreCycle trial.
Authors: Nadia Harbeck, Peter A. Fasching, Rachel Wuerstlein, Tom Degenhardt, Diana Lüftner, Ronald E. Kates, Johannes Schumacher, Philip Raeth, Oliver Hoffmann, Ralf Lorenz, Thomas Decker, Mattea Reinisch, Thomas Göhler, Peter Staib, Oleg Gluz, Timo Schinkoethe, Marcus Schmidt
Journal: Journal of Clinical Oncology (2023)

1008 Background: The multicenter, randomized phase IV Intergroup PreCycle trial (NCT03220178) evaluated the impact of CANKADO-based ePRO assessment on quality of life (QoL) in HR+/HER2- locally advanced or metastatic breast cancer (MBC) patients (pts) treated with palbociclib (P) and an aromatase inhibitor or P+fulvestrant. CANKADO PRO-React, an EU- registered medical device, is an autonomous application reacting to changes in pt self- reported QoL. Methods: Between 2017 and 2021, 499 pts (median age 59y) from 71 centers were randomized (2:1, stratified by therapy line) between an active (A; CANKADO PRO-React) or an inactive arm (B; inform; limited CANKADO functionality). 412 pts (271 A; 141 B) were available for analysis of the primary endpoint, i.e. time to deterioration (TTD) of QoL (10-point drop on FACT-G), using an Aalen-Johansen estimator for cumulative incidence function of TTD DQoL with 95% pointwise confidence intervals (CI). Secondary endpoints included PFS, OS, and DQoL (QoL deterioration). Results: In all pts (ITT-ePRO), a significantly decreased risk (HR 0.6982) for the CANKADO active arm A with 95% CI [0.5059, 0.9635] regarding DQoL was observed (p=0.03). In 1 st L pts (n=295), the decreased risk for arm A was 0.7162 (0.4839, 1.06; p=0.09), in 2 nd L pts (n=117) 0.6614 (0.3744, 1.168; p=0.2). Absolute pt numbers declined in later visits; until about visit 30, FACT- G completion rates were 80% and higher; mean total scores were similar between arms; the change from baseline showed a linear decline and a nearly constant offset in favor of arm A, particularly in 1 st L. No significant differences in clinical outcome were observed between arms: Median PFS (ITT population) was 21.4 (95% CI 19.4-23.7) (A) and 18.7 (15.1.-23.5) months (B); median OS was not reached (A) and 42.6 months (B). Conclusions: PreCycle is the first multicenter randomized eHealth trial demonstrating a significant benefit of an interactive autonomous patient empowerment application on QoL in MBC pts receiving oral tumor therapy. Clinical trial information: NCT03220178 .
Methods for selection of neoadjuvant treatment with chemotherapy for patients with hormone receptor-positive and HER2-negative with early breast cancer.
Authors: Ariadna Gasol Cudos, Serafin Morales Murillo, Noemí Tuset Der-abrain, Laura Arbones Cid, Ester Morera Morillo, Felip Vilardell, Douglas Sanchez Guzman, Carles Canosa Morales, Jordi Melé Olivé
Journal: Journal of Clinical Oncology (2023)

e12591 Background: Neoadjuvant chemotherapy (NCT) in hormone receptor positive and HER2 negative early breast cancer used to achieve a poor pathological response although patients with residual tumor inferior to 10 mm had a better significant survival. Methods: We analyzed the pathologic response (complete or major response if the residual tumor is inferior to 10 mm) in a consecutive series of 333 patients treated in our center considering clinicopathological classical variables, oncotype RS score, and non-response to previous sort course of hormonotherapy measured by the decrease in the Ki67 index. Results: Median age was of 51 years (24-87), median tumor size of 32mm (9-10) and 54% had nodal involvement. Pathologic complete response (pCR) was achieved in 16,5% and pathologic response according Symmans method type 0 and I in 33,6 %. Variables associated with pCR were initial tumor size &lt; 30 mm (OR: 0,409; p: 0,004), progesterone receptor &lt; 100 by histoscore (OR: 0,289; p: 0,00001) and Ki67 index &gt; 30 (OR: 2,23; p: 0,008). When these 3 variables have been associated, the pCR increases by 45%. When use the ONCOTYPE RS score to select patients to NCT the pCR found was 23,5% that increases to 42% if the RS score was superior to 32 in a series of 136 patients. Considering the RCB pathologic response, RS&gt;32 achieved a total of 73% of RCB 0-1 response. Finally, using the hormone non-response in patients with short course of hormonotherapy with non-decreases the Ki67 index, we found a 30% of pCR and 63% of RCB type 0-1 pathologic response. Conclusions: Selecting patients with early breast cancer with positive hormone receptors for neoadjuvant treatment with chemotherapy achieves a high response rate, going from 16% and reaching 40% in selected cases. The genomic platform and hormonal testing through Ki67 changes are very useful tools to select these patients. [Table: see text]
Therapy decision-making after pre-operative endocrine therapy in HR+ HER2- early breast cancer.
Authors: Irina Sorokina, Maria Ignatieva, Irina Vladimirovna Kolyadina, Gurami Kvetenadze, Maria Ivanyuk, Maria Gorbunova, Lyudmila Zhukova
Journal: Journal of Clinical Oncology (2023)

e12520 Background: Nowadays, the right way for therapy decision-making in HR+ HER2- early breast cancer (BC) includes the complex of validated multigene assays (VMA) result with clinical and IHC evaluation. Given the inability to use VMA in routine clinical practice, the short-term pre-operative endocrine therapy (P-ET) allows to estimate more precisely plan the further adjuvant therapy (AT) in the patients (pts) with early HR+ HER2- BC. Our work is aimed to share of pts with P-ET benefit, or tumor phenotype reversion for proper treatment planning in pts with early HR+ HER2- BC. Methods: HR+ HER2- BC pts stages I-II any level of Ki67 and any grade (G) have received P-ET (letrozole (L)/anastrozole (A)/tamoxifen (TAM)) no less than 2 weeks until surgery in A.S. Loginov MCSC, Russia. Enrollment period was Jun’20 - Jan’23. The study was aimed to access P-ET efficiency in pts with baseline Ki67&gt;10% downgrading to ≤10% (1), tumor ET sensitivity in the whole group (2) and/or phenotype transformation during P-ET followed by changing AT strategy (3). Results: At the data cut-off (Jan’23) 998 pts (5 pts were men) with HR+ HER2- BC were enrolled with median age 63,5 (range:26-85). The median time of P-ET was ≈19,5 days (range: 14-42). Pts flow according to tumor Ki67 level dynamic is show. 54% (434) pts with initially Ki67 level &gt;10% decreased Ki67≤10% after P-ET in whom 36% (314) pts avoided adjuvant chemotherapy. In Ki67≤10% baseline group (n=187) tumor Ki67 level after P-ET increased &gt;30% in every fifth case (n=35, 19%), that may reflect the initial ET resistance. Ki67 level dynamic change under P-ET was observed regardless of the TAM/IA use. 4% (38) pts has resulted the phenotype change to HER2+ BC (n=32) and TNBC (n=6) with subsequent AT decisions (anti-HER2-based or dose dense regimens, respectively). In this group there weren’t any Ki67 decrease after P-ET that additionally confirms the unmet need for treatment plan correction. Conclusions: In HR+ HER2- BC pts the results of P-ET with TAM or IA before surgery helps to estimate pts prognosis and further AT strategy: to identify the pts population of whom chemotherapy can be avoided while maintaining treatment efficacy with a better quality of life (1), to assess the initial ET tumor sensitivity (Ki67 baseline level independently) (2), to radically change the planned AT to achieve optimal treatment results (3). Mature data of long-term pts outcome are awaited. [Table: see text]